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The anti-secretory and anti-ulcer activities of esomeprazole in comparison with omeprazole in the stomach of rats and rabbits

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Abstract

Proton pump inhibitors (PPIs) are widely used to treat hyperacid secretion and stomach ulcers. The study investigated the anti-secretory and anti-ulcer effects of esomeprazole, the S-isomer of omeprazole on dimaprit, histamine and dibutyryl adenosine 3, 5 cyclic monophosphate (dbcAMP)-evoked gastric acid secretion, acidified ethanol (AE) and indomethacin (INDO)-induced haemorrhagic lesions and on prostaglandin E2 (PGE2) level in the rat in vivo and rabbit in vitro preparations. The effect of omeprazole was also investigated for comparison. Dimaprit-induced acid secretion was significantly (< 0.05) inhibited by both PPIs in a dose-dependent manner. In the isolated rabbit gastric glands, both PPIs elicited marked reductions in histamine- and dbcAMP-evoked acid secretion with similar potency. The lesions induced by either AE or INDO were significantly (< 0.05) reduced in the presence of either esomeprazole or omeprazole compared to control values. Increasing doses of esomeprazole before AE treatment resulted in a marked degree of cytoprotection and an elevation in the concentration of bound PGE2 in the stomach tissue homogenate. The results show that esomeprazole and omeprazole were equally effective against gastric haemorrhagic lesions induced by either AE or INDO and in inhibiting dimaprit-, dbcAMP- and histamine-induced gastric acid secretion in the rat and rabbit stomach both in vivo and in vitro. The gastro-protective effect of esomeprazole was found to be proportional to the bound PGE2 levels in the glandular area of the stomach.

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References

  1. Li X, Andersson TB, Ahlstrom M, Weidolf L (2004) Comparison of inhibitory effects of the proton pump inhibiting drugs omeprazole, esomeprazole, lansoprazole, pantoprazole and rabeprazole on human cytochrome P450 activities. Drug Metab Dispos 32:821–827

    Article  PubMed  CAS  Google Scholar 

  2. Larsson H, Carlsson E, Junggen U, Olbe L, Sjostrand SE, Skanberg I, Sundell G (1983) Inhibition of gastric secretion by omeprazole in the dog and rat. Gastroenterology 85:900–907

    PubMed  CAS  Google Scholar 

  3. Satoh H, Inatomi N, Nagaya H, Inada I, Nohara A, Nakamura H (1989) Antisecretory and antiulcer activities of a novel proton pump inhibitor AG-1749 in dogs and rats. J Pharmacol Exp Ther 248:806–815

    PubMed  CAS  Google Scholar 

  4. Nagaya H, Inatomi N, Ohara A, Satoh H (1991) Effects of the enantiomers of lansoprazole (AG-1749) on H+/K+-ATPase activity in canine gastric microsomes and acid formation in isolated canine parietal cells. Biochem Pharmacol 42:1875–1878

    Article  PubMed  CAS  Google Scholar 

  5. Sachs G, Kaunitz J, Mendlein J, Wallmark B (1989) Biochemistry of gastric acid secretion. In: Forte JG (Ed) Handbook of physiology, section 6; The Gastrointestinal system, Vol. 3: salivary, gastric and hepatobiliary secretion. American Physiological Society, Bethesda, pp 229–254

    Google Scholar 

  6. Miner PB, Katz PO, Chen Y (2003) Gastric acid control with esomeprazole, lansoprazole, omeprazole, pantoprazole, and rabeprazole: a five-way crossover study. Am J Gastroenterol 98:2616–2620

    Article  PubMed  CAS  Google Scholar 

  7. Goldstein JL, Johanson JF, Suchower LJ, Brown KA (2005) Healing of gastric ulcers with esomeprazole versus ranitidine in patients who continued to receive NSAID therapy: a randomized trial. Am J Gastroenterol 100:2650–2657

    Article  PubMed  CAS  Google Scholar 

  8. Robinson M (2001) New generation proton pump inhibitors: overcoming the limitations of early-generation agents. Eur J Gastroenterol Hepatol 13 (suppl 1):S43–47

    PubMed  Google Scholar 

  9. Johnson D (2003) Review of esomeprazole in the treatment of acid disorders. Expert Opin on Pharmacother 4:253–264

    Article  CAS  Google Scholar 

  10. Li ZS, Zhan XB, Xu GM, Chen NN, Liao Z (2007) Effect of esomeprazole and rabeprazole on intragastric pH in health Chinese: An open, randomized crossover trial. J Gastroenterol Hepatol 22 (6):815–820

    Article  PubMed  CAS  Google Scholar 

  11. Johnson DS, Stacy T, Ryan M, Wootton T, Willis J, Hornbuckle K, Brooks W, Doviak M (2005) A comparison of esomeprazole and lansoprazole for control of intragastric pH in patients with symptoms of gastro-oesophageal reflux disease. Aliment Pharmacol Ther 22:129–134

    Article  PubMed  CAS  Google Scholar 

  12. Fellenius E, Berglindh T, Sachs G (1981) Substituted benzimidazoles inhibit gastric secretion by blocking H+/K+-ATPase. Nature (Lond) 290:159–165

    Article  CAS  Google Scholar 

  13. Kobayashi T, Ohta Y, Inui K, Yoshino J, Nakazawa S (2002) Protective effect of omeprazole against acute gastric mucosal lesions induced by compound 48/80, a mast cell degranulator, in rats. Pharmacol Res 46:75–84

    Article  PubMed  CAS  Google Scholar 

  14. Thjodleifsson B (2002) Treatment of acid-related diseases in the elderly with emphasis on the use of proton pump inhibitors. Drugs Aging 19 (12):911–927

    Article  PubMed  CAS  Google Scholar 

  15. Berglindh T, Obrink KJ (1976) A method for preparing isolated glands from the rabbit gastric mucosa. Acta Physiol Scand 96 (2):150–159

    Article  PubMed  CAS  Google Scholar 

  16. Garner A, Chandranath I, Hasan MY, Bastaki SMA (1993) Relative merits of two novel antisecretory drugs acting via H+/K+ -ATPase inhibition and CCK receptors. Meeting Br Soc Gastroenterol 65:S17 (an abstract)

    Google Scholar 

  17. Berglindh T (1990) Gastric glands and cells: preparation and in vitro methods. Methods Enzymol 192:93–107

    PubMed  CAS  Google Scholar 

  18. Chandranath SI, Bastaki SMA, Singh J (2002) Comparative study on the activity of lansoprazole, omeprazole and PD-136450 on acidified ethanol- and indomethacin-induced gastric lesions in the rat. Clin Exp Pharmacol Physiol 29:173–180

    Article  PubMed  CAS  Google Scholar 

  19. Bastaki SMA, Chandranath SI, Singh J (2002) Comparison of the antisecretory and antiulcer activity of epidermal growth factor, urogastrone and transforming growth factor alpha and its derivative in rodents in vivo. Mol Cell Biochem 236:83–94

    Article  PubMed  CAS  Google Scholar 

  20. Bastaki SMA, Chandranath SI, Adem A (2004) The role of prostaglandin E2 in the ulcer preventing ability of leptin. Gut 53 (Suppl. 3):A77 (an abstract)

  21. Mercer DW, Cross JM, Barreto JC, Strobel NH, Russel DH, Miller TA (1995) Cholecystokinin is a potent protective agent against alcohol-induced gastric injury in the rat. Dig Dis Sci 40:651–660

    Article  PubMed  CAS  Google Scholar 

  22. Nishida A, Takinami Y, Yuki H, Kobayashi A, Akuzawa S, Kamata T, Ito H, Yamano M, Nagakura Y, Miyata K (1994) YM022{®-1-[2,3-dihydro-1-(2′-methylphenacyl)-2-oxo-5-phenyl-1H-1,4benzodiazepin-3-yl]-(methylphenyl)urea), a potent and selective gastrin/ cholecystokinin-B receptor antagonist, prevents gastric and duodenal lesions in rats. J Pharmacol Exp Ther 270:1256–1261

    PubMed  CAS  Google Scholar 

  23. Satoh H, Guth PH, Grossmann MI (1982) Role of food in gastrointestinal ulceration produced by indomethacin in the rat. Gastroenterology 32 (5):945–949

    CAS  Google Scholar 

  24. Adeyemi EO, Bastaki SMA, Chandranath SI, Hasan MY, Fahim M, Adem A (2005) Mechanism of action of leptin in preventing gastric ulcer. World J Gastroenterol 11(27):4154–4160

    PubMed  CAS  Google Scholar 

  25. Bastaki SMA, Chandranath I, Garner A (2000) Comparison of five antisecretory agents acting via gastric H+/K+-ATPase. J Physiol (Paris) 94:19–23

    Article  CAS  Google Scholar 

  26. Francis SH, Corbin JD (1994) Structure and function of cyclic nucleotide-dependent protein kinases. Annu Rev Physiol 56:237–272

    Article  PubMed  CAS  Google Scholar 

  27. Neer EJ, Clapham DE (1998) Roles of G protein subunits in transmembrane signaling. Nature 333:129–134

    Article  Google Scholar 

  28. Chew CS (1983) Inhibitory action of somatostatin on isolated gastric glands and parietal cells. Am J Physiol 245:G221-G229

    PubMed  CAS  Google Scholar 

  29. Bastaki SMA, Wallace JL (1999) Pathogenesis of nonsteroidal anti-inflammatory drug gastropathy: clues to preventive therapy. Can J Gastroenterol 13:123–127

    PubMed  CAS  Google Scholar 

  30. Wallace JL (2001) Pathogenesis of NSAID-induced gastroduodenal mucosal injury. Best Pract Res Clin Gastroenterol 15:691–703

    Article  PubMed  CAS  Google Scholar 

  31. Vane JR, Botting RM (1998) Mechanism of action of anti-inflammatory drugs. Int J Tissue React 20:3–15

    PubMed  CAS  Google Scholar 

  32. Schoen R, Vender R (1989) Mechanism of nonsteroidal anti-inflammatory drug-induced gastric damage. Am J Med 86:449–458

    Article  PubMed  CAS  Google Scholar 

  33. Jacobson ED, Chaudhury TK, Thompson WL (1976) Mechanism of gastric mucosal cytoprotection by prostaglandins. Gastroenterology 70:897–902

    Google Scholar 

  34. Choudhury TK, Jacobson ED (1978) Prostaglandin cytoprotection of gastric mucosa. Gastroenterology 74:59–63

    Google Scholar 

  35. Blandizzi C, Fornai M, Colucci R, Natale G, Lubrano V, Vassale C, Antonioli L, Lazzeri G, Tacca MD (2005) Lansoprazole prevents experimental gastric injury induced by non-steroidal anti-inflammatory drugs through a reduction of mucosal oxidative damage. World J Gastroenterol 11 (26):4052–4060

    PubMed  CAS  Google Scholar 

  36. Kasuya Y, Urushidani T, Okabe S (1979) Effects of various drugs and vagotomy on indomethacin-induced gastric ulcers in the rat. Jap J Pharmacol 29:670–673

    PubMed  CAS  Google Scholar 

  37. Ueki S, Takeuchi K, Okabe S (1988) Gastric motility is an important factor in the pathogenesis of indomethacin-induced gastric mucosal lesions in rats. Dig Dis Sci 33 (2):209–216

    Article  PubMed  CAS  Google Scholar 

  38. Lacy ER, Ito S (1982) Microscopic analysis of ethanol damage to rat gastric mucosa after treatment with a prostaglandin. Gastroenterology 83:619–625

    PubMed  CAS  Google Scholar 

  39. Szabo S, Trier J, Brown A (1985) Early vascular injury and increased vascular permeability in gastric mucosal injury caused by ethanol in the rat. Gastroenterology 88:228–236

    PubMed  CAS  Google Scholar 

  40. Whittle BJR (1983) Potentiation of taurocholate-induced rat gastric erosions following parenteral administration of cyclooxygenase inhibitors. Br J Pharmacol 80:545–551

    PubMed  CAS  Google Scholar 

  41. Pique JM, Whittle BJR, Esplugues JV (1989) The vasodilator role of endogenous nitric oxide in the rat gastric microcirculation. Eur J Pharmacol 174:293–296

    Article  PubMed  CAS  Google Scholar 

  42. Wallace JL, Tigley AW (1995) New insights into prostaglandins and mucosal defense. Aliment Pharmacol Ther 9:227–23

    Article  CAS  Google Scholar 

  43. Burget DW, Stephen G, Chiverton SG, Weinhold PA, Boland CR (1990) Is there an optimal degree of acid suppression for healing of duodenal ulcer? A model of the relationship between ulcer healing and acid suppression. Gastroenterology 99:345–351

    PubMed  CAS  Google Scholar 

  44. Scheiman JM, Kraus ER, Bonnville LA, Weinbold PA, Boland CR (1991) Synthesis and prostaglandin E2-induced secretion of surfactant phospholipids by isolated gastric mucous cells. Gastroenterology 100:1232–1240

    PubMed  CAS  Google Scholar 

  45. Yoshimura K, Kraus ER, Shimakura S, Scheiman JM, Boland CR (1992) Role of prostaglandin E2 in cholinergic-mediated glycoprotein synthesis in canine antrum. Dig Dis Sci 37:1045–1050

    Article  PubMed  CAS  Google Scholar 

  46. Hatlebakk JG (2003) Review article: gastric acidity—comparison of esomeprazole with other proton pump inhibitors. Aliment Pharmacol Ther 17(Suppl. 1):10–15

    Article  PubMed  CAS  Google Scholar 

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Correspondence to Salim M. A. Bastaki.

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Bastaki, S.M.A., Chandranath, I.S. & Singh, J. The anti-secretory and anti-ulcer activities of esomeprazole in comparison with omeprazole in the stomach of rats and rabbits. Mol Cell Biochem 309, 167–175 (2008). https://doi.org/10.1007/s11010-007-9657-5

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